Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
  • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
  • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
  • C07D451/06—Oxygen atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
  • C07C271/06—Esters of carbamic acids
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
  • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
  • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D211/40—Oxygen atoms
  • C07D211/42—Oxygen atoms attached in position 3 or 5
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
  • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
  • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D211/40—Oxygen atoms
  • C07D211/44—Oxygen atoms attached in position 4
  • C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
  • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems

Definitions

• X represents methylene or ethylene
• Y and Z taken alone, are the same or different and represent lower alkyl or arylalkyl or, taken together, form an alkylene residue
• the present invention also relates to a process for the preparation of such earbamates wherein 2-phenylbicyclo-(2,2,l)-heptane-2-carbonic acid chloride is reacted with an alkali metal azide such as potassium azide, preferably sodium azide, the azide so formed losing nitrogen to form the isocyanate, which is then reacted with an amino alcohol of the formula wherein R and R have the meaning given above.
• an alkali metal azide such as potassium azide, preferably sodium azide
• CH2 CH2 Z-dimethylamino ethanol, 3-dimethylaminopropanol or 3- diethylaminopropanol, 2-(4 methyl-piperazino)-ethanol, N-methyl-3-piperidinol, N-methyl-4-piperidinol, N-benzyl- 4-piperidinol, tropine, or chinuclidol-3 may, for example, be employed as suitable amino alcohols of the formula
• the alkali metal azide and the acid chloride are heated together in an inert aprotic organic solvent such as benzene, toluene or Xylene to the boiling point of the solvent (e.g., 50 C.200 C.), thus forming the azide.
• an inert aprotic organic solvent such as benzene, toluene or Xylene
• the reaction is completed in three to five hours.
• the carbamates are isolated by distilling off the solvent and may be converted into their salts by reaction with physiologically compatible acids, e.g. by contacting the reagents in an inert solvent. Hydrochloric acid, sulfuric acid, phosphoric acid, lactic acid, tartaric acid, maleic acid, fumaric acid and citric acid are all examples of physiologically compatible acids.
• the quaternary ammonium compounds may be produced by reacting the carbamates with suitable compounds such as a di-lower alkyl sulfate, preferably dimethyl sulfate or diethyl sulfate, for example by contacting the reagents in an inert solvent at room temperature or at an elevated temperature.
• suitable compounds such as a di-lower alkyl sulfate, preferably dimethyl sulfate or diethyl sulfate, for example by contacting the reagents in an inert solvent at room temperature or at an elevated temperature.
• the phenyl residue and the bicycloheptyl residue can assume either a cisor trans-position relative to the methyl bridge of the bicycloheptyl residue.
• the cis-position isomer is hereinafter referred to as the endo-form, and the transposition is hereinafter referred to as the exo-form.
• the new substances may be produced pure in both forms. If no reference is made to the form, mixtures of endoand eXo-form are concerned.
• Table 2 shows the quantities of active substances in accordance with the present invention which completely cure a nicotine-induced cramp in the isolated ileum of a guinea pig according to the method of R. Magnus, Pfluegers Arch. ges. Physiol. 102, 123 (1904).
• the new substances are administered orally or parenterally in doses of about 0.05 to 0.5 mg./kg. per day, suitably in combination with an inert physiologically acceptable solid or liquid carrier. Tablets and coated pills are particularly suitable for oral administration, while sterilized solutions may be used for parenteral administration, e.g., intravenous injection.
• excipient 49.90 mg. coating The excipient consists of 9 parts (by weight) of maize starch, 3 parts of lactose, and 1 part of Luviskol VA 64 (vinylpyrrolidone-vinyl acetate-mixed polymerizate 60:40, see Pharm. Ind. 1962, 586).
• the coating consists of parts (by weight) of crude sugar, 2 parts of maize starch, 2 parts of calcium carbonate and 1 part of talcum.
• EXAMPLE 5 3 chinuclidyl N [2 (2 phenylbicyclo (2,2,1)- heptyl)]-carbamate-methylsulfate (200 mg.) is dissolved in sterile physiological sodium chloride solution (1000 ml.). The solution is utilized in 1000 l-ml. ampules, which must be sterilised once more before use.
• Y XN/ X is methylene or ethylene; Y and Z are lower alkyl; R taken alone, is hydrogen; and R and R taken together with the nitrogen atom to which they are attached, represent a nitrogen heterocycle selected from the group consisting of N-methyl-piperidyl, N-benzyl-4-piperidyl, and 3-chinuclidyl.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Hydrogenated Pyridines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Nitrogen Condensed Heterocyclic Rings (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=5752147

Family Applications (1)

Country Status (14)

Cited By (6)

• 0
  • BE BE759460D patent/BE759460A/xx unknown
• 1969
  • 1969-11-26 DE DE1959365A patent/DE1959365C3/de not_active Expired
• 1970
  • 1970-01-25 AT AT10646/70A patent/AT303754B/de not_active IP Right Cessation
  • 1970-10-20 GB GB49667/70A patent/GB1272337A/en not_active Expired
  • 1970-11-02 IL IL35571A patent/IL35571A/xx unknown
  • 1970-11-12 NL NL7016572.A patent/NL166466C/xx not_active IP Right Cessation
  • 1970-11-13 CH CH1688270A patent/CH538453A/de not_active IP Right Cessation
  • 1970-11-18 FR FR707041404A patent/FR2073414B1/fr not_active Expired
  • 1970-11-23 YU YU2869/70A patent/YU34517B/xx unknown
  • 1970-11-24 US US00092517A patent/US3740405A/en not_active Expired - Lifetime
  • 1970-11-25 SE SE7015963A patent/SE370393B/xx unknown
  • 1970-11-25 CS CS795370A patent/CS158286B2/cs unknown
  • 1970-11-25 JP JP45104001A patent/JPS49831B1/ja active Pending
  • 1970-11-26 CA CA099,224A patent/CA945992A/en not_active Expired

Also Published As

Similar Documents